Comparison of treatments for the prevention of fetal growth restriction in obstetric antiphospholipid syndrome: a systematic review and network meta-analysis

Maria Letizia Urban,Alessandra Bettiol,Niccolò Lombardi,Claudia Ravaldi,Giacomo Emmi,Alfredo Vannacci,Caterina Serena,Irene Mattioli,Federico Mecacci,Gianni Virgili,Giada Crescioli,Elena Silvestri,Gerardo Di Scala,Laura Avagliano,Domenico Prisco

doi:10.1007/s11739-020-02609-4

Maria Letizia Urban, Alessandra Bettiol + Show 13 more

Open Access

https://doi.org/10.1007/s11739-020-02609-4

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Abstract

Women with criteria and non-criteria obstetric antiphospholipid syndrome (APS) carry an increased risk of pregnancy complications, including fetal growth restriction (FGR). The management of obstetric APS traditionally involves clinicians, obstetricians and gynaecologists; however, the most appropriate prophylactic treatment strategy for FGR prevention in APS is still debated. We performed a systematic review and network meta-analysis (NetMA) to summarize current evidence on pharmacological treatments for the prevention of FGR in APS. We searched PubMed and Embase from inception until July 2020, for randomized controlled trials and prospective studies on pregnant women with criteria or non-criteria obstetric APS. NetMA using a frequentist framework were conducted for the primary outcome (FGR) and for secondary outcomes (fetal or neonatal death and preterm birth). Adverse events were narratively summarised. Out of 1124 citations, we included eight studies on 395 pregnant patients with obstetric APS treated with low-dose aspirin (LDA) + unfractionated heparin (UFH) (n = 132 patients), LDA (n = 115), LDA + low molecular weight heparin (n = 100), LDA + corticosteroids (n = 29), LDA + UFH + intravenous immunoglobulin (n = 7), or untreated (n = 12). No difference among treatments emerged in terms of FGR prevention, but estimates were largely imprecise, and most studies were at high/unclear risk of bias. An increased risk of fetal or neonatal death was found for LDA monotherapy as compared to LDA + heparin, and for no treatment as compared to LDA + corticosteroids. The risk of preterm birth was higher for LDA + UFH + IVIg as compared to LDA or LDA + heparin, and for LDA + corticosteroids as compared to LDA or LDA + LMWH. No treatment was associated with an increased risk of bleeding, thrombocytopenia or osteopenia.

Highlights

Antiphospholipid syndrome (APS) is defined as the occurrence of thrombotic events and/or of recurrent pregnancy morbidity, in the presence of antiphospholipid antibodies, namely lupus anticoagulant (LA), anticardiolipin antibodies, or anti-β2 glycoprotein-I antibodies, detected on two or more occasions at least 12 weeks apart [1].In particular, obstetric APS is defined as the presence of aPL positivity and the occurrence of clearly set pregnancy complications, according to the current international criteria [2]
The association of low-dose aspirin (LDA) and heparin is known to increase live birth rate in obstetric APS women [32], no conclusive evidence exists on the relative benefits and risks of pharmacological interventions for the prevention of fetal growth restriction (FGR) in pregnant women with APS, and the use of LDA, heparin or their combination is still debated among clinicians
intravenous immunoglobulins (IVIg) intravenous immunoglobulin; LDA low dose aspirin; LMWH low molecular weight heparin; NC not calculable; UFH unfractionated heparin the 395 treated pregnancies [26.8%]

Summary

Introduction

Antiphospholipid syndrome (APS) is defined as the occurrence of thrombotic events (thrombotic APS) and/or of recurrent pregnancy morbidity (obstetric APS), in the presence of antiphospholipid antibodies (aPLs), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or anti-β2 glycoprotein-I (aβ2GPI) antibodies, detected on two or more occasions at least 12 weeks apart [1]. Obstetric APS is defined as the presence of aPL positivity and the occurrence of clearly set pregnancy complications, according to the current international criteria [2]. In real life, clinicians often face patients with aPL positivity presenting obstetric complications other than those mentioned in the classification criteria [2–6]. Patients with obstetric APS usually should plan pregnancy in accordance with clinicians and obstetrician–gynecologists, in order to set up the most appropriate pharmacological strategy in the period before, during and after pregnancy In the last 20 years the growing knowledge in the pathogenesis of APSmediated pregnancy complications and the improvement in the overall management of the disease have paved the way for obstetric APS women to consider the possibility of having children [8].

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